Background: It is estimated that 5-10% of Pakistani population is suffering from thyroid disorders. Depression and anxiety are two very common symptoms of hyperthyroidism and patients with these symptoms are often misdiagnosed as having any psychiatric disease. The objective of this study was to determine the prevalence of depression and anxiety among hyperthyroid patients in our population of Karachi, Pakistan. Methods: Cross-sectional study was conducted in which 200 patients visiting the outpatient department of Jinnah Postgraduate Medical Centre, Karachi, Pakistan, were inducted. Patients were classified as hyperthyroid and euthyroid. Convenient sampling technique was used. Data collection tool was a questionnaire in which sociodemographic questions and Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale were included. Logistic regression was used to determine the association of depression and anxiety with sociodemographic factors among hyperthyroid patients. Odds ratio (OR), 95% confidence interval (CI) and P values were calculated. Results: Depression and anxiety among hyperthyroid patients were found to be 84% and 58%, respectively. In multivariate analysis for hyperthyroid patients, age group of 18-40 years and females were more than two times (OR = 2.716, CI = 0.886-8.332), (OR = 2.587, CI = 0.827-8.095) depressed, compared to age group of 41-60 years and males, respectively, after adjusting for covariates. Similarly, females were found to have anxiety more than one times (OR = 1.771, CI = 0.720-4.356) compared to males while age group of 18-40 years was 30.5% (OR = 0.695, CI = 0.286-1.689) less likely to have anxiety compared to age group of 41-60 years. Conclusion: The results of this study revealed that depression and anxiety are a common finding among hyperthyroid patients. Therefore, hyperthyroidism should always be considered in the differential diagnosis of patients who present primarily with neuropsychiatric symptoms.

Thyroid disorders are very common affecting 750 million people worldwide by recent World Health Organization estimates, being possibly even more prevalent than diabetes. [1] All thyroid disease occurs more frequently in women than in men. The most common forms of hyperthyroidism include Grave's disease, toxic multinodular goiter, and toxic adenoma. Grave's disease, the most common of these has a male: female ratio of 15-10. It is estimated that 5-10% of Pakistani population is suffering from thyroid disorders. [2]

Hyperthyroidism is a set of disorders involving excess synthesis and secretion of the thyroid hormones, i.e., FT3, FT4 by the thyroid gland. Thyroid-stimulating hormone (TSH) produced by the pituitary gland maintains the levels of these hormones via a negative feedback mechanism. The excess of these unbound hormones in the peripheral circulation can cause thyrotoxicosis. These increased level of the hormones regardless of the etiology would result in increased transcription in cellular protein hence increased metabolic rate. The most common sign and symptoms of hyperthyroidism are nervousness, anxiety, increased perspiration, heat intolerance, weight loss despite an increased appetite, tremors, and palpitations.

It is well documented in the literature that the features of hyperthyroidism may be similar to those observed in patients with psychiatric disease. The most frequently features reported in common are depression and anxiety. [3] Numerous studies have been carried out in this regard. One study conducted in Rhode Island reported that 123 patients out of 170 presented with anxious mood. [4] In another study on patients with recently diagnosed untreated hyperthyroidism, depression, and anxiety was found in approximately one-third of the patients, bringing to the mind that concurrent presence of somatic thyroid symptoms artificially inflates the level of depression and anxiety. They also suggested that a psychiatrist should be careful to exclude patient with hyperthyroidism before primary psychiatric diagnosis. [5] One study in Turkey concluded that hyperthyroidism and syndromal depression and anxiety have overlapping features that can cause misdiagnosis during the acute phase. For differential diagnosis, one should follow-up patient with hyperthyroidism with specific hormonal treatment and evaluate persistent symptoms thereafter. [6] Rodewig stated that psychological symptoms in the hyperthyroidism are similar to neurotic anxiety symptomatology and anxious depression syndrome. [7]

Studies regarding the prevalence of hyperthyroidism have been conducted in Pakistan. One study comprising 500 participants, 77.2% were normal, 71% were hypothyroid, and 8.6% were diagnosed as hyperthyroid. [8] Another study determined the frequencies of thyroid problems in different age groups, sex and in different seasons. They reported that hyperthyroidism in all age groups was 5.1%. Prevalence of hyperthyroidism was higher in females (3.85%) than males (1.2%). [9]

There have been numerous studies in our region regarding thyroid disorders, but none has specifically targeted the neuropsychiatric symptoms in hyperthyroidism particularly depression and anxiety. This study of ours would highlight the above-mentioned symptoms in hyperthyroid patients and compare these with euthyroid individuals. This would give us an idea about how frequently depression and anxiety are associated with hyperthyroidism and would indicate the importance of suspecting hyperthyroidism in patients reporting to their GPs with these symptoms who are often wrongly diagnosed as having a psychiatric disease so that delays in diagnosis can be avoided. Moreover, this would help reduce the burden of the disease as well as the treatment cost.

Objective

To determine the prevalence of depression and anxiety and associated risk factors among hyperthyroid patients in the population of Karachi, Pakistan.

Hamilton Anxiety Rating Scale (HAM-A) is a 14 item rating scale designed to measure severity, symptoms, and pattern of anxiety. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where 14-17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. [13]

To make our comparisons more pronounced we labeled our HAM-D scoring as 0-7, no depression and >7, depression and our HAM-A scoring as 0-13, no anxiety and >13, anxiety.

Study setting

The study was carried out at Thyroid Clinic of Jinnah Postgraduate Medical Centre and Department of Atomic Energy in Karachi, Pakistan from June to December, 2015.

Study design

This was a cross-sectional study.

Inclusion and exclusion criteria

The study participants included individuals aged between 18 and 60 years. Subjects were classified according to their thyroid status. Previously diagnosed hyperthyroid patients having high level of FT3 (>7.8 pmol/L) and FT4 (>25 pmol/L) and suppressed level of TSH (<0.4 mU/L) were labeled as hyperthyroid whereas those having normal value of FT3 (3.5-7.8 pmol/L), FT4 (9.0-25.0 pmol/L) and TSH (0.4-4.5 mU/L) were labeled euthyroid. [14] The patients with known psychiatric disorders were excluded. We also excluded patients with chronic diseases such as diabetes and tuberculosis and uncooperative patients as well as those with language barriers.

Data collection tool

Participants were interviewed after getting written consent. Instrument used was a validated questionnaire which comprised three sections. Section A was related to sociodemographic characteristics, Section B was the HAM-D and Section C was the HAM-A to assess respective symptoms in both groups. The HAM-A and the HAM-D were both developed by Max Hamilton in 1959 and 1960, respectively. These are standard scales used by clinicians to assess and rate the severity of a patient's anxiety and depression, respectively. The questionnaire was prepared in English and for the sake of consistency, was translated to Urdu.

Variables

The two dependent variables used were anxiety and depression whereas the independent variables were age, gender, occupation, marital status, residence, and education.

Sample size

We used the formula, nz 2p (100 − p)/d2 × (n − 1) + z2p × (100 − p) for calculating the sample size which came out to be 497 but due to time restraints we had to limit our sample size to 200, i.e., 100 hyperthyroid and 100 euthyroid individuals. We also reviewed previous studies in which their sample size was on average 95 hyperthyroid patients and an equal proportion of euthyroid individuals.

Sampling technique

Nonprobability convenient sampling was used.

Data management and statistical analysis

Epidata software was used for data entry. Data were cleaned and coded after which Statistical Package for Social Sciences (SPSS) for version 16 was used for data analysis. Frequencies of the sociodemographic characteristics were calculated. Comparison was done between sociodemographic characteristics and anxiety and depression, both for hyperthyroid and euthyroid individuals. Chi-square was run and their significance was assessed. Univariate and multivariate analysis was also performed in which odds ratio (OR) and confidence interval (CI) was calculated. To exhibit the proportions of the HAM-D and HAM-A items, Pie charts were made in Microsoft Excel. EndNote for windows was used for citations.

Ethical considerations

First, study protocol was approved by the parent institution. Permission letters were signed from the respective authorities concerned. The study participants were initially informed about the nature and objective of this study and how their participation would benefit the community. Thereafter, they were made to sign a written consent form after being ensured about the confidentiality of the information they provide.

Results

Mean age of participants was 33.9 ± 11.883 (standard deviation). 73.5% participants were of age group 18-40 years, 68% were females, 70.5% were married, 44% were housewives, and 76% were literate. Seventy percent of hyperthyroid individuals took less than an year to seek treatment after they initially experienced symptoms and 70% were correctly diagnosed within an year of seeking treatment [Table 1].

In hyperthyroid group, 84% participants were depressed out of which 61% were of age group 18-40 years, 64% were females, 57% were literate and 59% took less than an year to seek treatment after initially experiencing symptoms. In euthyroid group, 30% participants had depression, in which 21% were of age 18-40 years, 19% were females and 26% were literate [Table 2].

Table 2: Comparison* between sociodemographic characteristics and depression among hyperthyroid and euthyroid groups

In hyperthyroid group, 58% people had anxiety. Majority (38%) was of age group 18-40 years, 45% were females, 37% were literate and 41% took less than an year to seek treatment after initially experiencing symptoms. While in euthyroid group, 90% people had no anxiety, and only 10% of them were identified to have anxiety out of which 8% were of age group 18-40 years, 6% were females and all of them were literate [Table 3].

Table 3: Comparison* between sociodemographic characteristics and anxiety among hyperthyroid and euthyroid groups

In univariate analysis for hyperthyroid individuals, those in age group of 18-40 years were more than two times (OR = 2.652, CI = 0.891-7.896) more likely to have depression than age group of 41-60 years and females were also more than two times (OR = 2.489, CI = 0.822-7.537) more likely to have depression than males [Table 4]. Similarly, females were found to have anxiety more than one times (OR = 1.731, CI = 0.711-4.215) than males while age group of 18-40 years was 32.6% (OR = 0.674, CI = 0.281-1.618) less likely to have anxiety compared to age group of 41-60 years [Table 5]. However, all these figures were statistically insignificant. There was no significant association of sociodemographic variables with depression and anxiety in euthyroid group [Table 4] and [Table 5].

In multivariate analysis for hyperthyroid individuals, age group of 18-40 years was more than two times (OR = 2.716, CI = 0.886-8.332) more likely to have depression and females were also more than two times (OR = 2.587, CI = 0.827-8.095) more likely to be depressed after adjusting for covariates [Table 6]. Similarly, females were found to have anxiety more than one times (OR = 1.771, CI = 0.720-4.356) while age group of 18-40 years was 30.5% (OR = 0.695, CI = 0.286-1.689) less likely to have anxiety compared to age group of 41-60 years [Table 7]. There was no significant association of sociodemographic variables with depression and anxiety in euthyroid group [Table 6] and [Table 7] on multivariate analysis as well.

Regarding symptoms of depression, there was significant difference between hyperthyroid and euthyroid groups in terms of, loss of interest in work and activities, loss of weight, and gastrointestinal symptoms [Figure 1].

This study revealed that the symptoms of anxiety and depression were found in greater abundance among hyperthyroid patients when compared to euthyroid. Insomnia, autonomic symptoms, anxious mood, and tension were also found in a significantly larger number of hyperthyroid participants.

Among hyperthyroid group in our study, patients between 18 and 40 years were more prone to have symptoms of depression (OR = 2.65, CI = 0.891-7.896). Mean age of the study participants was 33.9, standard deviation: 11.883. Females were more likely to have depression when compared to their male counterparts (OR = 2.587, CI = 0.827-8.095). Similar statistics were found in another study according to which, 68% of the hyperthyroid patients among the group were females, mean age being 47 ± 14.8. [8] Hyperthyroid patients who were literate were more likely to have depression and anxiety (OR = 1.642, CI = 0.553-4.877) than those who were illiterate.

In this study, 84% hyperthyroid had depression whereas 58% had anxiety in varying degrees of severity, i.e., mild, moderate, and severe. The figures were significantly low among euthyroid controls, 16% of which had no depression whereas, 90% of euthyroid individuals had no anxiety. In concordance with our study, anxiety disorder number of symptoms and depression disorder number of symptoms in another study was also higher among hyperthyroid patients when compared to euthyroid individuals. [8] This is because of the fact that high levels of serum T3 and T4 has a negative impact on a person's psychological well being. Serum T4 levels in the upper range of normal or slightly higher have been reported in depressed patients as compared to healthy or psychiatric controls. [15]

Among symptoms of depression reported by most hyperthyroid patients in our study included depressed mood (87%), loss of interest in daily work and activities (72%), loss of weight (68%), and somatic gastrointestinal symptoms (61%). It is also reported in certain studies that hyperthyroidism is an etiologic factor for depression and symptoms of anxiety. [16],[17] In another study, it was reported that symptoms related to a high level of serum thyroid hormones is directly related to anxiety severity. [18]

It was found in our study that 80% of the hyperthyroid patients suffered from symptoms of somatic anxiety, 84% of hyperthyroid patients had psychological anxiety and 87% complained of having depressed mood. A study conducted previously had reported that prevalence rate of major depression was 13-19%, generalized anxiety disorder was 46-61% and panic disorder was 30-61% among hyperthyroid patients. [7],[18] A lot of these patients seeked medical help primarily because of the somatic and mood symptoms.

Many participants complained of having symptoms, like forgetfulness, difficulty concentrating in work and difficulty in carrying out everyday tasks. Frequent mood swings experienced by patients had a significant impact in their social life and marital life, with many complaining of having strained interpersonal relationships since their disease. These symptoms were so severe in certain patients that they had to quit their work.

Recommendation

It is necessary for medical practitioners to take into account the neuropsychiatric symptoms when treating a hyperthyroid patient. Appropriate medication for the management might be necessary depending on the severity of the symptoms.

Strengths

To the best of our knowledge, studies highlighting the importance of depression and anxiety in hyperthyroidism and comparing it with that of euthyroid individuals have not been conducted in Pakistan, Karachi in particular. This study would serve as a source to emphasize the significance of anxiety and depression among the patients of hyperthyroidism in Pakistan.

Limitations

Since we are conducting this study as students and without any significant financial funding, our budget was limited due to which we could not conduct a large, multisector study. We had to limit the sample size due to our restricted time frame.

Conclusion

According to our study, neuropsychiatric symptoms such as, depression and anxiety were found in a significantly higher number of hyperthyroid patients as compared to euthyroid controls.